XB-ART-39925
Cancer Biol Ther
2008 Dec 01;712:1867-74. doi: 10.4161/cbt.7.12.6945.
Show Gene links
Show Anatomy links
Apoptosis and tumor resistance conferred by Par-4.
Zhao Y
,
Rangnekar VM
.
???displayArticle.abstract???
Par-4 is a tumor suppressor protein with a pro-apoptotic function. Epigenetic silencing of Par-4 is seen in diverse tumors and Par-4 knockout mice develop spontaneous tumors in various tissues. Endogenous Par-4 is essential for sensitization of cells to diverse apoptotic stimuli, whereas ectopic expression of Par-4 can selectively induce apoptosis in cancer cells. The cancer-specific pro-apoptotic action of Par-4 resides in its centrally located SAC domain. This review emphasizes the role of Par-4/SAC in apoptosis and tumor resistance. SAC transgenic mice display normal development and life span, and, most importantly, are resistant to spontaneous, as well as oncogene-induced, autochthonous tumors. The tumor resistant phenotype and undetectable toxicity of SAC in vivo suggests the SAC domain possesses tremendous therapeutic potential.
???displayArticle.pubmedLink??? 18836307
???displayArticle.pmcLink??? PMC2683365
???displayArticle.link??? Cancer Biol Ther
???displayArticle.grants??? [+]
CA105453 NCI NIH HHS , CA60872 NCI NIH HHS , CA84511 NCI NIH HHS , R01 CA060872-11 NCI NIH HHS , R01 CA105453-05 NCI NIH HHS , R01 CA116658-04 NCI NIH HHS , R01 CA060872 NCI NIH HHS , R01 CA105453 NCI NIH HHS , R01 CA116658 NCI NIH HHS , R01 CA084511 NCI NIH HHS
Species referenced: Xenopus laevis
Genes referenced: pawr
References [+] :
Affar,
Targeted ablation of Par-4 reveals a cell type-specific susceptibility to apoptosis-inducing agents.
2006, Pubmed
Affar, Targeted ablation of Par-4 reveals a cell type-specific susceptibility to apoptosis-inducing agents. 2006, Pubmed
Balducci, Cancer and age in the USA. 2001, Pubmed
Balmain, Cancer as a complex genetic trait: tumor susceptibility in humans and mouse models. 2002, Pubmed
Balmain, Cancer: new-age tumour suppressors. 2002, Pubmed
Bargou, Constitutive nuclear factor-kappaB-RelA activation is required for proliferation and survival of Hodgkin's disease tumor cells. 1997, Pubmed
Barradas, The downregulation of the pro-apoptotic protein Par-4 is critical for Ras-induced survival and tumor progression. 1999, Pubmed
Berra, Positioning atypical protein kinase C isoforms in the UV-induced apoptotic signaling cascade. 1997, Pubmed
Bieberich, Regulation of cell death in mitotic neural progenitor cells by asymmetric distribution of prostate apoptosis response 4 (PAR-4) and simultaneous elevation of endogenous ceramide. 2003, Pubmed
Blaschke, Widespread programmed cell death in proliferative and postmitotic regions of the fetal cerebral cortex. 1996, Pubmed
Boehrer, Deregulated expression of prostate apoptosis response gene-4 in less differentiated lymphocytes and inverse expressional patterns of par-4 and bcl-2 in acute lymphocytic leukemia. 2001, Pubmed
Boghaert, Immunohistochemical analysis of the proapoptotic protein Par-4 in normal rat tissues. 1997, Pubmed
Bos, ras oncogenes in human cancer: a review. 1989, Pubmed
Chakraborty, Par-4 drives trafficking and activation of Fas and Fasl to induce prostate cancer cell apoptosis and tumor regression. 2001, Pubmed
Chang, p62 forms a ternary complex with PKCzeta and PAR-4 and antagonizes PAR-4-induced PKCzeta inhibition. 2002, Pubmed
Cheema, Par-4 transcriptionally regulates Bcl-2 through a WT1-binding site on the bcl-2 promoter. 2003, Pubmed
Cook, Decreased expression of the pro-apoptotic protein Par-4 in renal cell carcinoma. 1999, Pubmed
Danial, Cell death: critical control points. 2004, Pubmed
Diaz-Meco, Inactivation of the inhibitory kappaB protein kinase/nuclear factor kappaB pathway by Par-4 expression potentiates tumor necrosis factor alpha-induced apoptosis. 1999, Pubmed
Downward, PI 3-kinase, Akt and cell survival. 2004, Pubmed
Duan, Prostate apoptosis response-4 production in synaptic compartments following apoptotic and excitotoxic insults: evidence for a pivotal role in mitochondrial dysfunction and neuronal degeneration. 1999, Pubmed
Duan, Participation of par-4 in the degeneration of striatal neurons induced by metabolic compromise with 3-nitropropionic acid. 2000, Pubmed
Díaz-Meco, The product of par-4, a gene induced during apoptosis, interacts selectively with the atypical isoforms of protein kinase C. 1996, Pubmed
El-Guendy, Identification of a unique core domain of par-4 sufficient for selective apoptosis induction in cancer cells. 2003, Pubmed
Feuerhake, NFkappaB activity, function, and target-gene signatures in primary mediastinal large B-cell lymphoma and diffuse large B-cell lymphoma subtypes. 2005, Pubmed
Fleischer, Modulating apoptosis as a target for effective therapy. 2006, Pubmed
Galang, Oncogenic Ras can induce transcriptional activation through a variety of promoter elements, including tandem c-Ets-2 binding sites. 1994, Pubmed
García-Cao, "Super p53" mice exhibit enhanced DNA damage response, are tumor resistant and age normally. 2002, Pubmed
García-Cao, Tumour-suppression activity of the proapoptotic regulator Par4. 2005, Pubmed
Gary, Ischemic and excitotoxic brain injury is enhanced in mice lacking the p55 tumor necrosis factor receptor. 1998, Pubmed
Goswami, Binding and phosphorylation of par-4 by akt is essential for cancer cell survival. 2005, Pubmed
Guo, Prostate apoptosis response-4 enhances secretion of amyloid beta peptide 1-42 in human neuroblastoma IMR-32 cells by a caspase-dependent pathway. 2001, Pubmed
Gurumurthy, Phosphorylation of Par-4 by protein kinase A is critical for apoptosis. 2005, Pubmed
Hurwitz, The TRAMP mouse as a model for prostate cancer. 2001, Pubmed
Ionov, Mutational inactivation of the proapoptotic gene BAX confers selective advantage during tumor clonal evolution. 2000, Pubmed
Jemal, Cancer statistics, 2006. 2006, Pubmed
Jiang, Cellular caspase-8-like inhibitory protein (cFLIP) prevents inhibition of muscle cell differentiation induced by cancer cells. 2006, Pubmed
Johnstone, A novel repressor, par-4, modulates transcription and growth suppression functions of the Wilms' tumor suppressor WT1. 1996, Pubmed
Johnstone, Mapping of the human PAWR (par-4) gene to chromosome 12q21. 1998, Pubmed
Kawai, ZIP kinase triggers apoptosis from nuclear PML oncogenic domains. 2003, Pubmed
Kimura, Tumor necrosis factor-alpha and Fas activate complementary Fas-associated death domain-dependent pathways that enhance apoptosis induced by gamma-irradiation. 2000, Pubmed
Kyprianou, Programmed cell death during regression of PC-82 human prostate cancer following androgen ablation. 1990, Pubmed
Kögel, Dlk/ZIP kinase-induced apoptosis in human medulloblastoma cells: requirement of the mitochondrial apoptosis pathway. 2001, Pubmed
Lafuente, Regulation of mature T lymphocyte proliferation and differentiation by Par-4. 2003, Pubmed
Lo, Allelic variation in gene expression is common in the human genome. 2003, Pubmed
Loo, Apoptosis is induced by beta-amyloid in cultured central nervous system neurons. 1993, Pubmed
Maier, Modulation of mammalian life span by the short isoform of p53. 2004, Pubmed
Majumder, Prostate intraepithelial neoplasia induced by prostate restricted Akt activation: the MPAKT model. 2003, Pubmed
Makin, Apoptosis and cancer chemotherapy. 2000, Pubmed
Marte, PKB/Akt: connecting phosphoinositide 3-kinase to cell survival and beyond. 1997, Pubmed
Martikainen, Programmed death of nonproliferating androgen-independent prostatic cancer cells. 1991, Pubmed
Mattson, Par-4: an emerging pivotal player in neuronal apoptosis and neurodegenerative disorders. 1999, Pubmed
Mattson, Activation of NF-kappaB protects hippocampal neurons against oxidative stress-induced apoptosis: evidence for induction of manganese superoxide dismutase and suppression of peroxynitrite production and protein tyrosine nitration. 1997, Pubmed
Moreno-Bueno, Inactivation of the candidate tumor suppressor par-4 in endometrial cancer. 2007, Pubmed
Nalca, Oncogenic Ras sensitizes cells to apoptosis by Par-4. 1999, Pubmed
Niwa, Efficient selection for high-expression transfectants with a novel eukaryotic vector. 1991, Pubmed
Page, Interaction partners of Dlk/ZIP kinase: co-expression of Dlk/ZIP kinase and Par-4 results in cytoplasmic retention and apoptosis. 1999, Pubmed
Paige, Redefining tumour suppressor genes: exceptions to the two-hit hypothesis. 2003, Pubmed
Pedersen, The prostate apoptosis response-4 protein participates in motor neuron degeneration in amyotrophic lateral sclerosis. 2000, Pubmed
Pikarsky, NF-kappaB functions as a tumour promoter in inflammation-associated cancer. 2004, Pubmed
Qiu, Mutually exclusive expression patterns of Bcl-2 and Par-4 in human prostate tumors consistent with down-regulation of Bcl-2 by Par-4. 1999, Pubmed
Ranganathan, Regulation of cancer cell survival by Par-4. 2005, Pubmed
Rao, Growth, body weight, survival, and tumor trends in (C57BL/6 X C3H/HeN) F1 (B6C3F1) mice during a nine-year period. 1990, Pubmed
Rayet, Aberrant rel/nfkb genes and activity in human cancer. 1999, Pubmed
Roussigne, THAP1 is a nuclear proapoptotic factor that links prostate-apoptosis-response-4 (Par-4) to PML nuclear bodies. 2003, Pubmed
Scharnhorst, WT1 proteins: functions in growth and differentiation. 2001, Pubmed
Sells, Commonality of the gene programs induced by effectors of apoptosis in androgen-dependent and -independent prostate cells. 1994, Pubmed
Shareef, Role of tumor necrosis factor-alpha and TRAIL in high-dose radiation-induced bystander signaling in lung adenocarcinoma. 2007, Pubmed
Taglialatela, Evidence for DNA fragmentation in the CNS of aged Fischer-344 rats. 1996, Pubmed
Tartaglia, A novel domain within the 55 kd TNF receptor signals cell death. 1993, Pubmed
Tyner, p53 mutant mice that display early ageing-associated phenotypes. 2002, Pubmed
Vitaterna, Differential regulation of mammalian period genes and circadian rhythmicity by cryptochromes 1 and 2. 1999, Pubmed
Vivanco, The phosphatidylinositol 3-Kinase AKT pathway in human cancer. 2002, Pubmed
Vojtek, Mammalian Ras interacts directly with the serine/threonine kinase Raf. 1993, Pubmed
Williams, Molecular regulation of apoptosis: genetic controls on cell death. 1993, Pubmed
Xie, Aberrant induction of Par-4 is involved in apoptosis of hippocampal neurons in presenilin-1 M146V mutant knock-in mice. 2001, Pubmed
Yan, Allelic variations in gene expression. 2004, Pubmed
Zhao, Cancer resistance in transgenic mice expressing the SAC module of Par-4. 2007, Pubmed